Possible active tubular secretion of sulfamonomethoxine and its metabolites in pigs.

Abstract

The effect of probenecid on the plasma kinetics of sulfamonomethoxine (SMM) was examined in conscious pigs. A linear kinetic dose of SMM (10 mg/kg) was injected with or without probenecid. Probenecid (25 mg/kg, i.v.) was injected immediately before SMM injection and against at 1, 2, 3, 4 and 6 h later. The AUCs of SMM and of the acetylated compound of SMM (AcSMM) in probenecid injected animals were significantly larger when compared with those of non-injected animals (p less than 0.05). Next, possible active secretion from the renal tubule of SMM and its metabolites was examined using probenecid and pyrazinoate. Ten commercial pigs with ureter cannulae were used under anesthesia. The plasma concentration of SMM and AcSMM was maintained at a steady state by a priming dose of SMM (5 mg/kg, i.v.) followed by sustaining infusion (4 micrograms/kg/min). Renal clearance of AcSMM was suppressed by bolus injection of probenecid (25 mg/kg), but that of SMM was not. The renal excretion of a water soluble metabolite was suppressed by probenecid. No marked changes in renal excretory kinetics were found by pyrazinoate injection (12.5 mg/kg, i.v.). Consequently, the saturation in the active tubular secretion of AcSMM may play an important role in the nonlinear pharmacokinetics of SMM in pigs.